WO2022218970A3 - Conjugués de pyrrolobenzodiazépine - Google Patents

Conjugués de pyrrolobenzodiazépine Download PDF

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Publication number
WO2022218970A3
WO2022218970A3 PCT/EP2022/059730 EP2022059730W WO2022218970A3 WO 2022218970 A3 WO2022218970 A3 WO 2022218970A3 EP 2022059730 W EP2022059730 W EP 2022059730W WO 2022218970 A3 WO2022218970 A3 WO 2022218970A3
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WO
WIPO (PCT)
Prior art keywords
pyrrolobenzodiazepine conjugates
pyrrolobenzodiazepine
conjugates
formula
unit
Prior art date
Application number
PCT/EP2022/059730
Other languages
English (en)
Other versions
WO2022218970A2 (fr
Inventor
Philip Wilson Howard
Luke Masterton
Arnaud Charles Tiberghien
Ian Hutchinson
Stephen John Gregson
Thais CAILLEAU
Original Assignee
Medimmune Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medimmune Limited filed Critical Medimmune Limited
Publication of WO2022218970A2 publication Critical patent/WO2022218970A2/fr
Publication of WO2022218970A3 publication Critical patent/WO2022218970A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6855—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from breast cancer cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68035—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a pyrrolobenzodiazepine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6863—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from stomach or intestines cancer cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne un conjugué de formule (I) : L - (DL)p, L étant une unité ligand (c'est-à-dire un agent de ciblage), p valant de 1 à 20, DL étant une unité de liaison de médicament de formule (I'); RLL étant un lieur pour la liaison à l'unité de ligand, D représentant D1; D' représentant D'1.
PCT/EP2022/059730 2021-04-12 2022-04-12 Conjugués de pyrrolobenzodiazépine WO2022218970A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB2105187.5A GB202105187D0 (en) 2021-04-12 2021-04-12 Pyrrolobenzodiazepine conjugates
GB2105187.5 2021-04-12

Publications (2)

Publication Number Publication Date
WO2022218970A2 WO2022218970A2 (fr) 2022-10-20
WO2022218970A3 true WO2022218970A3 (fr) 2022-12-29

Family

ID=75949628

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2022/059730 WO2022218970A2 (fr) 2021-04-12 2022-04-12 Conjugués de pyrrolobenzodiazépine

Country Status (2)

Country Link
GB (1) GB202105187D0 (fr)
WO (1) WO2022218970A2 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013177481A1 (fr) * 2012-05-25 2013-11-28 Immunogen, Inc. Benzodiazépines et leurs conjugués
WO2014057074A1 (fr) * 2012-10-12 2014-04-17 Spirogen Sàrl Pyrrolobenzodiazépines et leurs conjugués
WO2020079229A1 (fr) * 2018-10-19 2020-04-23 Medimmune Limited Conjugués de pyrrolobenzodiazépine
WO2020205564A1 (fr) * 2019-03-29 2020-10-08 Immunogen, Inc. Dérivés de bis-benzodiazépine cytotoxiques et leurs conjugués avec des agents de liaison à une cellule pour inhiber la croissance cellulaire anormale ou pour traiter des maladies prolifératives

Family Cites Families (16)

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JPS58180487A (ja) 1982-04-16 1983-10-21 Kyowa Hakko Kogyo Co Ltd 抗生物質ｄｃ−８１およびその製造法
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
PL2270010T3 (pl) 2004-03-01 2012-07-31 Medimmune Ltd Pochodne 11-hydroksy-5h-pirolo[2,1-c][1,4]benzodiazepin-5-onu jako kluczowe związki pośrednie do otrzymywania c2 podstawionych pirolobenzodiazepin
BRPI0516284A (pt) 2004-09-23 2008-09-02 Genentech Inc anticorpo construìdo com cisteìna, método de selecionar anticorpos, compostos conjugados de droga-anticorpo, composição farmacêutica, método para matar ou inibir a proliferação de células de tumor, métodos de inibir a proliferação celular e o crescimento de células de tumor, artigo manufaturado e método para produzir um composto
NZ563136A (en) 2005-04-21 2009-11-27 Spirogen Ltd Pyrrolobenzodiazepines
RS52060B (en) 2006-01-25 2012-04-30 Sanofi CYTOTOXIC AGENTS CONTAINING NEW TOMAIMYCIN DERIVATIVES
JP5290276B2 (ja) 2007-05-08 2013-09-18 ジェネンテック， インコーポレイテッド システイン改変抗ｍｕｃ１６抗体および抗体−薬物結合体
WO2009052249A1 (fr) 2007-10-19 2009-04-23 Genentech, Inc. Anticorps anti-tenb2 modifiés par des cystéines et conjugués anticorps-médicament
EA024730B1 (ru) 2010-04-15 2016-10-31 Медимьюн Лимитед Пирролбензодиазепиновые соединения, их конъюгаты, фармацевтические композиции, содержащие указанные конъюгаты, и применение указанных конъюгатов
FR2967466B1 (fr) 2010-11-16 2014-10-24 Renault Sa Procede de detection des defauts de combustion d'un moteur a combustion interne
GB201106173D0 (en) 2011-04-12 2011-05-25 Adc Biotechnology Ltd System for purifyng, producing and storing biomolecules
EA031585B1 (ru) 2012-12-21 2019-01-31 Медимьюн Лимитед Пирролобензодиазепины и их конъюгаты
CN106459205B (zh) 2014-04-11 2021-04-09 免疫医疗有限责任公司 包含半胱氨酸工程化抗体的轭合化合物
GB201607478D0 (en) 2016-04-29 2016-06-15 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
KR20190083654A (ko) 2016-11-10 2019-07-12 메디뮨 엘엘씨 Asct2에 특이적인 결합 분자 및 이의 용도
CN112203696A (zh) 2018-05-25 2021-01-08 免疫医疗有限公司 吡咯并苯并二氮杂*缀合物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013177481A1 (fr) * 2012-05-25 2013-11-28 Immunogen, Inc. Benzodiazépines et leurs conjugués
WO2014057074A1 (fr) * 2012-10-12 2014-04-17 Spirogen Sàrl Pyrrolobenzodiazépines et leurs conjugués
WO2020079229A1 (fr) * 2018-10-19 2020-04-23 Medimmune Limited Conjugués de pyrrolobenzodiazépine
WO2020205564A1 (fr) * 2019-03-29 2020-10-08 Immunogen, Inc. Dérivés de bis-benzodiazépine cytotoxiques et leurs conjugués avec des agents de liaison à une cellule pour inhiber la croissance cellulaire anormale ou pour traiter des maladies prolifératives

Non-Patent Citations (4)

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Title
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GREGSON STEPHEN J ET AL: "Synthesis and evaluation of pyrrolobenzodiazepine dimer antibody-drug conjugates with dual [beta]-glucuronide and dipeptide triggers", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 179, 18 June 2019 (2019-06-18), pages 591 - 607, XP085772542, ISSN: 0223-5234, [retrieved on 20190618], DOI: 10.1016/J.EJMECH.2019.06.044 *
KATIE E. ARCHER ET AL: "Synthesis of Highly Potent N-10 Amino-Linked DNA-Alkylating Indolinobenzodiazepine Antibody-Drug Conjugates (ADCs)", ACS MEDICINAL CHEMISTRY LETTERS, vol. 10, no. 8, 22 July 2019 (2019-07-22), pages 1211 - 1215, XP055705444, ISSN: 1948-5875, DOI: 10.1021/acsmedchemlett.9b00254 *
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WO2022218970A2 (fr) 2022-10-20
GB202105187D0 (en) 2021-05-26

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